Molecular mechanism and structural models of protein-mediated copper transfer to the Arabidopsis thaliana ethylene receptor ETR1 at the ER membrane.

In plants, the gaseous plant hormone ethylene regulates a wide range of developmental processes and stress responses. The small unsaturated hydrocarbon is detected by a family of receptors (ETRs) located in the membrane of the endoplasmic reticulum, which rely on a monovalent copper cofactor to detect this hydrocarbon. The copper-transporting P-type ATPase RAN1 (HMA7), located in the same membrane, is known to be essential for the biogenesis of ETRs. Still, the precise molecular mechanism by which the receptors acquire their copper cofactor remains unclear. A recent study by our laboratory demonstrated a direct interaction between RAN1 and soluble copper chaperones of the ATX1 family with the model ethylene receptor ETR1, providing initial insights into the mechanism by which copper is transferred from the cytosol to the membrane-bound receptors. In this study, we further investigated these interactions with respect to the function of individual domains in complex formation. To this end, we combined biochemical experiments and computational predictions and unraveled the processes and mechanisms by which copper is transferred to ETR1 at the molecular level.